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Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer

Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer: A Phase II, Multicenter, Single-Arm Study

This study is a prospective, multicenter, single-arm, open-label phase II clinical trial.

It is planned to enroll 53 subjects with HER2-expressing (IHC 1+, 2+, or 3+) partially platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (defined as disease recurrence occurring ≥6 months and <12 months after the completion of the last platinum-containing therapy).

The study adopts a two-stage sequential treatment strategy:

Stage 1: All enrolled subjects will receive Trastuzumab Rezetecan (4.8 mg/kg IV, Q3W) combined with Bevacizumab (7.5 mg/kg IV, Q3W). Trastuzumab Rezetecan will be administered for a maximum of 1 year, or until disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria are met, whichever occurs first; Bevacizumab will be continued until disease progression, unacceptable toxicity, or other protocol-defined reasons.

Stage 2: Upon confirmed disease progression in Stage 1, subjects will enter Stage 2 to receive platinum-based chemotherapy (e.g., Carboplatin + Paclitaxel, Carboplatin + Liposomal Doxorubicin, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may replace Carboplatin in cases of intolerance, including but not limited to these regimens, determined by the investigator) until subsequent disease progression or unacceptable toxicity.

The primary objective is to evaluate progression-free survival 1 (PFS1) of SHR-A1811 combined with bevacizumab based on RECIST v1.1. Secondary objectives include objective response rate (ORR), disease control rate (DCR), progression-free survival 2 (PFS2), overall survival (OS), and safety and tolerability.

研究概览

研究类型

介入性

注册 (估计的)

53

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100000
        • Peking University Cancer Hospital & Institute

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 75年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

女性

描述

Inclusion Criteria:

  1. Voluntarily agree to participate in the study, provide written informed consent, demonstrate good compliance, and be able to cooperate with protocol-required follow-up visits.

  2. Female patients aged 18 to 75 years old (inclusive, calculated from the date of signing the informed consent form).

  3. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (mucinous carcinoma is excluded).

  4. Received 1 to 2 prior lines of systemic therapy and must have received prior PARP inhibitor therapy.

  5. Partially platinum-sensitive recurrence, defined as disease recurrence occurring ≥6 months but <12 months after the completion of the last platinum-containing therapy:

    • Neoadjuvant and/or adjuvant therapy are combined and counted as 1 line of therapy;
    • Maintenance therapy does not count as a separate line of therapy;
    • Changes in treatment regimens due to reasons other than disease progression (such as intolerable toxicity) are considered part of the same line of therapy and are not counted separately.
  6. Confirmed HER2 expression status: IHC 1+, 2+, or 3+.

  7. At least one measurable lesion according to RECIST v1.1 criteria (longest diameter ≥10 mm on spiral CT scan, or short axis ≥15 mm for lymph nodes).

  8. ECOG performance status (PS) score: 0 to 1..

  9. Expected life expectancy ≥12 weeks.

  10. Adequate function of vital organs.

Exclusion Criteria:

  1. Central nervous system (CNS) metastasis: Untreated or active CNS metastases. Subjects are eligible if CNS metastases have received adequate local therapy (e.g., surgery or radiotherapy), neurological symptoms have returned to baseline (excluding residual signs or symptoms related to CNS treatment), and clinical stability has been maintained for ≥ 4 weeks prior to the first dose.
  2. Second primary malignancy, except for the following: adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma; or other malignancies that have been adequately treated with curative intent and have shown no evidence of recurrence or metastasis for >= 2 years prior to the first dose.
  3. Uncontrolled pleural effusion or ascites. Subjects are eligible if therapeutic drainage has been performed and clinical stability has been maintained for at least 2 weeks after drainage.
  4. Severe pulmonary disease: History of interstitial lung disease (ILD) or non-infectious pneumonitis (such as radiation pneumonitis) requiring systemic corticosteroid therapy; current or suspected ILD, non-infectious pneumonitis, or other active pulmonary inflammation; or significant pulmonary impairment including severe asthma, severe chronic obstructive pulmonary disease (COPD), or restrictive lung disease within 6 months prior to the first dose.
  5. Tuberculosis infection: Active pulmonary tuberculosis infection. Subjects who have received adequate and standard anti-tuberculosis therapy and have discontinued anti-tuberculosis treatment for >= 3 months prior to the first dose are eligible.
  6. Uncontrolled cardiovascular disease: Poorly controlled or serious cardiovascular disease, including but not limited to unstable angina, symptomatic congestive heart failure (NYHA Class II-IV), acute myocardial infarction within 6 months prior to the first dose, or unstable arrhythmias requiring clinical intervention within 1 month prior to the first dose.
  7. High-risk gastrointestinal indications (perforation/fistula): Gastrointestinal perforation, gastrointestinal fistula, tracheoesophageal fistula, urethral fistula, or abdominal abscess occurring within 3 months prior to the first dose, or judged by the investigator to have a high risk of occurrence in the near future. Subjects who have undergone definitive treatments such as artificial stoma or ureteral stent placement and are evaluated by the investigator as clinically stable are eligible.
  8. Active infection: Severe infection occurring within 1 month prior to the first dose; any active infection requiring systemic intravenous antimicrobial therapy; or unexplained fever (> 38.5 deg C) from the screening period up to the first dose.
  9. Specific prior drug exposure: Prior treatment with antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, or prior single-agent topoisomerase I inhibitor therapy (such as irinotecan, topotecan).
  10. Drug hypersensitivity: Known hypersensitivity to any active ingredient or excipient of Trastuzumab Rezetecan (SHR-A1811), including the antibody, payload SHR169265, and linker; known hypersensitivity to any component of Bevacizumab, or a history of severe hypersensitivity reactions.
  11. Other comprehensive risks: Any clinical condition that, in the opinion of the investigator, may increase the risk to the subject, interfere with the interpretation of study results, or preclude compliance with the study protocol.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Sequential Treatment Group

Stage 1: SHR-A1811 (4.8 mg/kg, IV) + Bevacizumab (7.5 mg/kg, IV), Q3W, until disease progression or intolerable toxicity. Stage 2: Upon confirmed progression in Stage 1, subjects proceed to receive investigator's choice of platinum-based chemotherapy rechallenge until subsequent progression or intolerable toxicity.

Humanized anti-HER2 IgG1 monoclonal antibody conjugated with a topoisomerase I inhibitor payload (SHR169265). Administered IV at 4.8 mg/kg on Day 1 of each 21-day cycle.

Recombinant humanized anti-VEGF monoclonal antibody. Administered IV at 7.5 mg/kg on Day 1 of each 21-day cycle (dosing interval >30 min after SHR-A1811).

Platinum-based chemotherapy rechallenge administered in Stage 2, selected by the investigator based on patient clinical condition (including but not limited to: Carboplatin + Paclitaxel ± Bevacizumab, Carboplatin + Pegylated Liposomal Doxorubicin ± Bevacizumab, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may be substituted if carboplatin is not tolerated).

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
PFS1
大体时间:From the first dose of study treatment up to approximately 36 months.

Progression-Free Survival 1 (PFS1) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Defined as the time from the date of the first dose of study treatment to the date of first documented objective tumor progression or death due to any cause, whichever occurs first.

From the first dose of study treatment up to approximately 36 months.

次要结果测量

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间:Up to approximately 36 months.

Defined as the proportion of subjects who achieve a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) based on RECIST v1.1 criteria.

Up to approximately 36 months.
Disease Control Rate (DCR)
大体时间:Up to approximately 36 months.

Defined as the proportion of subjects who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) based on RECIST v1.1 criteria.

Up to approximately 36 months.
Progression-Free Survival 2 (PFS2)
大体时间:Up to approximately 36 months.

Defined as the time from the date of the first dose of study treatment in Stage 1 to the second documented objective disease progression or death due to any cause, whichever occurs first.

Up to approximately 36 months.
Overall Survival (OS)
大体时间:Up to approximately 36 months.

Defined as the time from the date of the first dose of study treatment to death due to any cause, calculated in the intent-to-treat (ITT) population.

Up to approximately 36 months.
Safety and Tolerability
大体时间:From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).

Incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs) graded according to NCI-CTCAE v5.0 criteria, as well as the proportion of dose interruptions, dose reductions, and treatment discontinuations due to treatment-related toxicities.

From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年10月22日

初级完成 (估计的)

2028年9月30日

研究完成 (估计的)

2029年9月30日

研究注册日期

首次提交

2026年9月20日

首先提交符合 QC 标准的

2026年9月20日

首次发布 (实际的)

2026年9月28日

研究记录更新

最后更新发布 (实际的)

2026年10月1日

上次提交的符合 QC 标准的更新

2026年9月28日

最后验证

2026年9月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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